Knowledge of interactions between neurons is requisite to an understanding of retinal function. The ability to identify cells on the basis of the neuroactive substances they contain provides an opportunity to elucidate chemical-specific pathways. In the proposed project, intracellular filling of identified retinal neurons will be combined with a variety of light and electron microscopic histochemical and immunohistochemical techniques to reveal the functional microcircuitry of identified neurons in the vertebrate retina. These studies will focus on (1) a centrifugal pathway projecting to the retina from the olfactory system onto dopaminergic interplexiform cells in the fish retina, and (2) the ON-OFF directionally selective ganglion cells in turtle and rabbit retina. Amacrine cell targets of the centrifugal pathway will be identified on the basis of transmitter class and morphologic subclass. The arrangement of the input onto the dendritic tree of individual members of the target amacrine cell types will be mapped out. Two identified peptides are found in centrifugal fibers. An unknown, third, non-peptide neuroactive substance is indicated that will be identified. Central projections from the olfactoretinalis will be examined to determine their identity and afferent or efferent nature. Using autoradiographic and biochemical techniques, the nature and localization of receptors from the centrifugal peptides will be determined, and the physiologic role of centrifugal peptide release will be explored via horizontal and ganglion cell recording. The identity and arrangement of synaptic inputs to dopaminergic interplexiform cells will be elucidated by dual intracellular filling after immunologic identification. Finally, the arrangement of acetylcholine and GABA inputs onto the dendritic tree of individual, characterized, directionally selective ganglion cells in rabbit and turtle retina will be described. The overall goal is to define the retinal circuitry underlying basic aspects of visual processing common to all vertebrates, including humans.